PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma

Autor: Dave Johnson, Peter Martin, Christopher R. Flowers, Wayne R. Godfrey, Martin Dreyling, Brad S. Kahl, Gilles Salles, Pier Luigi Zinzani, Nina D. Wagner-Johnston, Sven de Vos, Kristie A. Blum, Langdon L. Miller, Daniel Li, Ajay K. Gopal, Andreas Viardot, Roger Dansey, Leanne Holes, Andre Goy, Stephen J. Schuster, Ian W. Flinn, Wojciech Jurczak, Andrew Davies
Přispěvatelé: A. K. Gopal, B. S. Kahl, S. d. Vo, N. D. Wagner-Johnston, S. J. Schuster, W. J. Jurczak, I. W. Flinn, C. R. Flower, P. Martin, A. Viardot, K. A. Blum, A. H. Goy, A. J. Davie, P. L. Zinzani, M. Dreyling, D. Johnson, L. L. Miller, L. Hole, D. Li, R. D. Dansey, W. R. Godfrey, G. A. Salles
Jazyk: angličtina
Rok vydání: 2014
Předmět:
antagonists /&/ inhibitors
Disease-Free Survival
Double-Blind Method
Female
Humans
Kaplan-Meier Estimate
Lymph Node
medicine.medical_specialty
adverse effects/therapeutic use
Quinazolinone
Follicular lymphoma
pathology
Lymphocyte Count
Lymphoma
Non-Hodgkin
Gastroenterology
Lymphoplasmacytic Lymphoma
chemistry.chemical_compound
immune system diseases
Internal medicine
hemic and lymphatic diseases
Indolent Non-Hodgkin Lymphoma
medicine
drug therapy/mortality/pathol/ogy
Male
Middle Aged
Neoplasm Grading
Purine
Copanlisib
business.industry
General Medicine
medicine.disease
Adult
Aged
Aged
Lymphoma
Surgery
adverse effects/therapeutic use
chemistry
80 and over
Class Ia Phosphatidylinositol 3-Kinase
adverse effects/therapeutic use
Recurrence
neoplastic Agent
Rituximab
Refractory Follicular Lymphoma
business
Idelalisib
medicine.drug
Popis: Background Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin’s lymphomas. Methods In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin’s lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety. Results The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin’s lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenstrom’s macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin’s lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%). Conclusions In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin’s lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424.)
Databáze: OpenAIRE
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